Flow cytometry is a bioanalysis technique that enables counting and sorting of cells and particles based on their physical and biochemical properties. Flow cytometer instruments are widely used in diverse research and clinical settings, for example the diagnosis and/or study of leukemia, HIV, and stem cell biology. Due to the technology employed, current flow cytometers are immobile, bulky, and very expensive to purchase ($50k-$600k) and operate, meaning that these instruments are typically found only in centralized core facilities. Access to such facilities is limited or unavailable to researchers and clinicians in small labs, at the point-of-care, or in remote locations such as rural areas or far-forward combat zones. This proposed project combines cutting edge lab-on-a-chip technology (microfluidics, optics, microacoustics) with expertise in research applications in cancer and other fields to develop a breakthrough flow cytometer that is 1/100 the size and cost of conventional instruments while meeting or surpassing their performance standards. The NanoSort device employs inexpensive, mass-manufacturable chips that can be discarded after a single use, a valuable feature in circumstances requiring sterile conditions or involving biohazardous samples. The project objectives entail three specific aims, namely (1) demonstration of current alpha prototype utility in cancer research application;(2) development of beta prototype chip using new materials with improved mechanical features (such as cell flow rate) and mass-manufacturability;and (3) significantly increased cell detection and sorting rates via improvements to existing proprietary signal processing algorithms. This new technology will bring flow cytometry to small labs, point-of-care clinics, remote locations, and additional markets not served by conventional instrumentation that is bulky, immobile, and prohibitively expensive, thereby accelerating the pace of scientific discovery in diverse fields including cancer research, stem cell biology, genomics, and more. Further, the development of this affordable, portable, easy-to-maintain, and high performance flow cytometry system will fulfill humanitarian missions (for example, disease diagnosis and monitoring in developing countries). This work serves the public by offering a sophisticated and broadly applicable technology resource to new users in diverse clinical and research contexts, and creates business growth opportunities by opening new markets for reagent manufacturers and assay developers. PUBLIC HEALTH RELEVANCE: The proposed project aims to build a prototype cytometer that integrates various patented technologies (integrated photonic, acoustic, and microfluidic lab-on-a-chip technology and software). This prototype will be mass-manufacturable and will have capabilities for cell detection and sorting at rates comparable to leading industry machines that are large (non-portable and centralized) and prohibitively expensive to most researchers and clinicians. This new fully developed cytometer will serve demands for decentralized, inexpensive tools for cutting edge research applications in diverse fields including cancer, stem cell biology, immunology, pathology, and epigenetics.